This Laboratory Program is part of a major group in the discovery of novel antitumor agents from natural sources. It is dedicated to terrestrial plants as potential sources of novel antitumor agents. Plants will primarily be acquired from the semi-arid U.S. Southwest and Western United States. A diversity of plant families and genera will be sought in order to maximize the chemical diversity available in the plant kingdom, thereby increasing the chances for positive results during the course of this investigation. An additional added criterion will be to search out rare and previously unexplored plant species. Once the plant materials have been received, they will be processed to provide crude materials for antitumor testing in a variety of the group's in vitro screens. Sufficiently active plants will be tested also for in vivo activity and subsequently subjected to bioassay directed fractionation and isolation and characterization of the active component(s). Approximately 400 plants per year (800 extracts) will be sent to Wayne State University for assay. Subsequent fractionation and purification of lead extracts, estimated at 2% or 8 plants will generate another 100- 200 extracts. Also, we presently have about 30 leads whose fractionation will begin upon initiation of the Program. This proposal outlines a workplan for analyzing selected species of the U.S. Southwest and West as potential sources of naturally-occurring antitumor drugs or synthons. This effort will also require plans for scaling-up the production of these compounds, either through range management or the development of specialty cash crops. This research component will include the training of graduate students and post-doctoral fellows in the growing and processing of plant materials, the isolation and identification of the active compounds, and large scale production of these specialty chemicals. In this manner the results of this research effort will add to the technology required for the development of sustainable agrisystems for arid and semi-arid lands.